In general, Dr. Lechleiter's laboratory is interested in the molecular and cellular mechanisms of neuroprotection that occur in response to ischemic stress, acute brain injury and aging. Recent advances in their laboratory revealed how natural healing mechanisms could be activated by boosting mitochondrial energy (ATP) production in astrocytes, the major support cell in the brain. Their approach is substantially different from other neuroprotective strategies that have thus far proven unsuccessful. A strategy that increases energy production is inherently robust, since multiple protective processes benefit.

One specific area of research is an investigation of the underlying protective mechanisms mediated by stimulation of purinergic P2Y1 receptors, which are primarily expressed on astrocytes.
A second major research project is an examination of the neuroprotective efficacy of thyroid hormones via stimulation of fatty acid oxidation (FAO), which appears to occur predominantly in astrocytes.
A third area of research is focused on the long-term neurological consequences of repetitive traumatic brain injury (TBI). Finally, Dr. Lechleiter's laboratory is investigating the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the development of age-associated neurological deficits.

Discovery leads to patent for novel method of treating traumatic brain injuryA researcher in the School of Medicine at The University of Texas Health Science Center at San Antonio, Professor James Lechleiter, received a U.S. patent (No. 8,618,074) Dec. 31 for his discovery that a class of compounds is protective against traumatic brain injury (TBI). The experimental test tissues pictured were obtained from a 60-year-old human patient who had undergone a temporal lobectomy to relieve epilepsy. Neurons are visible in red, astrocytes (caretaker cells) in green. The specimen on the right was placed in a solution containing 2-methylthio-ADP, one of a class of compounds called purinergic receptor ligands. The specimen on the left was placed in untreated solution. The specimens are shown five days after ischemic trauma that usually results in killing of neurons and astrocytes. 2-methylthio-ADP preserved many neurons and astrocytes in the treated specimen.

Spiral Ca2+ waves in Xenopus oocyte Movie
Intracellular Ca2+ is a ubiquitous second messenger that controls the activity of a multitude of enzymatic processes. Ca2+ cannot be metabolized in a manner that is analogous to the cycle of protein phosphorylation / de-phosphorylation. Rather, Ca2+ signals are mediated by changes in concentration of the ion. Studies in our laboratory revealed spiral waves of intracellular Ca2+ release induced by inositol 1,4,5 trisphosphate (IP3) (Figure 2). Spiral waves are the trademark pattern formations of excitable media and have been described in other systems such as the classic Belousov-Zhabotinsky chemical reaction, aggregating slime mold, and electrical activity in neuronal tissue. The active propagation of Ca2+ release in the form of Ca2+ waves provides an efficient mechanism to communicate hormonal signals over long distances.

Dr. Lechleiter lectures primarily to graduate students on biophysics, cell biology and neurobiology as well as the fundamental principles of light microscopy. Since 2009, he has lectured in "Fundamentals in Biomedical Sciences" (INTD 5000), which is the core course for all incoming IMGP / IBMS graduate students. He developed the curriculum for the Imaging Week module and was a lecturer on ER Stress in the Obesity Week module. He currently directs "Practical Optical Microscopy" (CSBL 5083), which is widely attended by not only students, but by faculty and staff. He also continues to lecture in multiple courses that are generally offered on an annual basis including Biology of Aging (CSBL 6048), Molecular, Cellular and Developmental Neuroscience (INTD 5040), Advanced Cell and Molecular Biology (INTD 5007), Methods in Cell Biology Course (CSBL 5007), Cell Signaling Mechanisms (INTD 6033) and Advanced Molecular Cell Biology (MMED 6016). As can be discerned by the course numbers, these lectures were given in multiple departments and programs. Finally, the Henry Stewarts talks online (www.hstalks.com) created a video of his lecture "Impact of mitochondria on astrocyte neuroprotection in video series entitled: "The Physiology and Pathophysiology of Neuroglia".

He has also provided research training and mentoring at the high school, undergraduate, graduate, post-doctoral and research assistant professor levels. Overall, he has directed 2 MS thesis, 10 Ph.D. dissertations (4 are active, 2 URMs) and 10 post-doctoral fellows. Moreover, he has supervised 33 rotation graduate students, 10 undergraduate students and 7 high school students. He has been a member of the supervising committees of over 50 Ph.D. dissertations and 11 Master's theses.